Can cadmium trigger estrogen-related responses in laboratory-grown breast cancer cells?

Details

In laboratory cell-culture experiments, researchers studied how cadmium affects the estrogen receptor and other estrogen-regulated genes in the human breast cancer cell line MCF-7.

Treating MCF-7 cells with 1 μM cadmium decreased estrogen receptor levels by 58%, alongside a 62% decrease in estrogen receptor mRNA. Progesterone receptor levels increased 3.2-fold after cadmium treatment. This increase was blocked by the anti-estrogen ICI-164,384. Cadmium also increased progesterone receptor mRNA and cathepsin D mRNA.

An in vitro nuclear transcription run-on assay showed that cadmium increased transcription of the progesterone receptor and pS2 genes while decreasing transcription of the estrogen receptor gene. The researchers reported that these were not general effects of heavy metals: zinc at 25 and 100 μM did not affect progesterone receptor protein or mRNA levels.

In a clone of MDA-MB-231 cells transfected with the human estrogen receptor, cadmium stimulated pS2 and progesterone receptor mRNAs. It had no effect in MDA-MB-231 cells transfected with antisense estrogen receptor. Cadmium also stimulated an estrogen response element in transient transfection experiments.

These data suggest that cadmium's effects are mediated by the estrogen receptor independently of estradiol. Beyond its effects on gene expression, cadmium stimulated MCF-7 cell growth 5.6-fold.